Keywords
Dysautonomia - Medulloblastoma - paroxysmal sympathetic hyperactivity - Pediatric
brain tumors
Introduction
Paroxysmal sympathetic hyperactivity (PSH) is a group of symptoms and signs suggestive
of episodic autonomic hyperactivity and is not a very well-recognized entity in pediatric
oncology as most reports are following acquired traumatic brain injury. There are
also some published data of sympathetic hyperactivity in children with infections
related to the brain. Although rare, an index of suspicion is important in the early
diagnosis of this syndrome and this ultimately affects the long-term outcome. We report
the case of a child with medulloblastoma with PSH.
Case Report
A 9 year old girl who presented with cerebellar signs was diagnosed with medulloblastoma
(sonic hedgehog type)-standard risk after undergoing surgery for a fourth ventricle
tumor. Although adjuvant chemoradiotherapy was advised, her parents did not comply
with the treatment. Six months later, she had recurrence of symptoms and imaging confirmed
relapse. She underwent a second debulking surgery but had persistent cerebellar signs.
Four weeks after surgery, she was started on craniospinal radiotherapy.
After the first fraction of radiation, she developed persistent hiccups, tachycardia
(>140), tachypnea, and hypertension (>95th centile). Supportive treatment with metoclopramide and baclofen improved symptoms
for a short while and radiotherapy was continued.
After 1 week under radiation treatment, she presented with recurrent paroxysmal episodes
of lethargy. Observations showed persistent tachycardia, tachypnea, hypertension,
fever, and dystonia of the neck. Evaluation showed features suggestive of subacute
intestinal obstruction with evidence of dilated bowel loops. Supportive treatments
including correction of anemia with packed cell transfusion, possible sepsis with
antibiotics, and bowel rest were initiated. Calcium channel blockers were started,
but controlling hypertension was difficult. Investigations including renal function,
liver function, electrolytes, and blood cultures were normal. Computed tomography
pulmonary angiography did not show any evidence of pulmonary embolism. In view of
difficulty in controlling symptoms, sympathetic hyperactivity was considered as a
differential diagnosis and centrally acting sympathomimetic (clonidine) with a beta-blocker
(propranolol) was initiated. There was a dramatic response in the control of signs
and symptoms. The clinical picture and response to treatment favored a final diagnosis
of PSH. She was continued on radiation and completed the treatment protocol without
any major issues.
Discussion
PSH has been described in literature since 1954, known as autonomic seizures.[1] With more evidence emerging in the early 21st century, PSH became recognized as a definite entity though known by several names
such as dysautonomia,[2]
[3] hypothalamic midbrain dysregulation syndrome, autonomic storming, autonomic diencephalic
epilepsy, and paroxysmal sympathetic instability with dystonia. Later, a consensus
identified a name for the entity “paroxysmal sympathetic hyperactivity,” which was
specific, was not preempting an underlying pathophysiology, and accurately portrayed
the conceptual definition.[4]
PSH affects approximately 8%–10% of patients with acquired brain injuries, causing
significant morbidities.[5] Apart from traumatic brain injury, other nontraumatic causes include brain tumors,
infections, encephalitis, metabolic disorders, and hypoxic ischemic injury.[6]
[7] Very little published data are available on childhood brain tumors. Goh et al. had described the phenomenon which developed within a week following resection of
a midbrain glioma in a 7-year-old child and lasted for 6 months.[8] In children, there are some old reports of diencephalic autonomic epilepsy caused
by a diencephalic neoplasm and arachnoid cyst.[9] Our child developed PSH following surgery and at the start of radiotherapy.
PSH has a host of possible signs and symptoms of sympathetic overactivity including
increased body temperature, heart rate, respiratory function, blood pressure, sweating,
agitation, muscle posturing (decerebrate and decorticate), and hypertonia (spasticity,
rigidity, or dystonia). Previously, the presentation of five or more of the following
symptoms was considered diagnostic of PSH: tachypnea, tachycardia, hyperthermia, hypertension,
diaphoresis, dystonia, and decerebrate and decorticate posturing. In 2014, a PSH Consensus
Working Group was formed for defining the various aspects of PSH. They put forward
a clinical feature scale (CFS scale) [Table 1] and a diagnostic likelihood tool (DLT) [Table 2] for early diagnosis of PSH. A diagnostic likelihood score combining CFS and DLT
more than 17 made the diagnosis of PSH more probable.[4] However, this score is not validated in children and a modified score needs to be
formulated.
Table 1
Paroxysmal sympathetic hyperactivity assessment measure, clinical feature scale
|
Score
|
0
|
1
|
2
|
3
|
|
Heart rate
|
<100
|
100-119
|
120-139
|
>140
|
|
Respiration
|
<18
|
18-23
|
24-29
|
>30
|
|
Systolic pressure
|
<140
|
140-159
|
160-179
|
>180
|
|
Temperature (°C)
|
<37
|
37-37.9
|
38-38.9
|
>39.0
|
|
Sweating
|
No obvious sweat
|
Wet skin (mild)
|
Beads of sweat (moderate)
|
Profuse sweating (severe)
|
|
Posture at attack
|
No changes in muscular tone
|
Slightly increased muscular tone, flexible limbs (mild)
|
Increased muscular tone, hard to flex limbs (moderate)
|
Rigid and inflexible limbs (severe)
|
|
Severity of clinical features
|
Nil
|
Mild
|
Moderate
|
Severe
|
|
Total Score
|
0
|
1-6
|
7-12
|
>13
|
Table 2
Paroxysmal sympathetic hyperactivity assessment measure, diagnostic likelihood tool
|
Parameter
|
|
Score
|
|
CFS – Clinical feature scale; DLT – Diagnostic likelihood tool
|
|
Clinical features occur simultaneously
|
1
|
|
Paroxysmal episodes
|
1
|
|
Sympathetic overreactivity to painless stimuli
|
1
|
|
Clinical features occur for >3 consecutive days
|
1
|
|
Clinical features persist for >2 weeks following brain injury
|
1
|
|
Clinical features persist after treatment of alternative differential diagnosis
|
1
|
|
Number of attacks in a day >2
|
1
|
|
Absence of parasympathetic neural symptoms during attacks
|
1
|
|
No other presumed cause of clinical features
|
1
|
|
Antecedent-acquired brain injury
|
1
|
|
PSH diagnostic likelihood
|
Unlikely
|
Likely
|
Very likely
|
|
Total score (CFS + DLT)
|
<8
|
8-16
|
>17
|
In a child undergoing chemotherapy and radiotherapy, infectious processes such as
pneumonia, sepsis, urinary tract infection and pulmonary embolism needs to be ruled
out. Other differential diagnoses suggested are neuroleptic malignant syndrome, drug
fever, seizure, rhabdomyolysis, and narcotic withdrawal. Development of symptoms may
have a temporal relation to painful stimuli, suctioning, bathing, repositioning, etc.
Constipation, distended bladder, abdominal distension, increased respiratory secretions,
infections, pressure sore, or just an intravenous cannulation can trigger PSH. In
our child, the only trigger we could identify was constipation following vincristine
administration.
Pathophysiology of this condition is not clear. Initially thought to be epileptogenic
in nature (autonomic epilepsy), no activity was seen in an electroencephalography.
Current theories include conventional disconnection and excitatory: inhibitory ratio
model which is an excessive adrenergic activity due to either disruption of pathways
between the cortex and hypothalamus, which activates central excitatory foci around
the diencephalon (thalamus and hypothalamus), or due to damage to the central inhibitory
structures. In brain tumors, the additional etiology of autoimmunity also has been
suggested.[10]
Immediate treatment of PSH is determining the urgency of control of symptoms. An algorithm
has been suggested [Figure 1].[11] For children with airway, breathing, or circulation issues, administration of intravenous
diazepam at a dose of 0.05–0.2 mg/kg/dose is recommended. Some authors have recommended
clonazepam, hydroxyzine, and delorazepam. Use of intravenous morphine for poor response
or intolerance to benzodiazepines has been suggested followed by addressing the precipitating
conditions such as pain, constipation, or bladder distension. In a nonurgent situation,
commonly advocated medications are beta-blockers (propranolol), central alpha blockers
(clonidine), bromocriptine, gabapentin, benzodiazepine, medications for hyperthermia
(baclofen and dantrolene), and opiates. Environmental modifications such as controlling
the temperature of the room, limiting conversations inside the room, restricting visitors,
and listening calm music have been suggested. Trying to have lights on during the
day and reversing the same at night to establish regular sleep–awake cycle can limit
the development of PSH.
Figure 1: Clinical management algorithm for paroxysmal sympathetic hyperactivity
Since PSH in children is associated with severe brain injury (low Glasgow Coma Scale),
it has been associated with worse clinical outcome, prolonged periods of hospital
stay, and intensive care support. Significance of the same in pediatric brain tumors
needs to be studied. Uncontrolled sympathetic activity can lead to hemodynamic instability,
neurogenic pulmonary edema, significant loss of weight, inadequate nutrition, and
electrolyte imbalances. Abnormal posturing and dystonia increases the risk of heterotopic
ossification. Early diagnosis and timely management has an impact on the long-term
outcome.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
